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© Research
Publication : Cell reports

Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5α Binding to the Viral Core.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell reports - 17 Mar 2020

Selyutina A, Persaud M, Simons LM, Bulnes-Ramos A, Buffone C, Martinez-Lopez A, Scoca V, Di Nunzio F, Hiatt J, Marson A, Krogan NJ, Hultquist JF, Diaz-Griffero F,

Link to Pubmed [PMID] – 32187548

Link to DOI [DOI] – S2211-1247(20)30274-610.1016/j.celrep.2020.02.100

Cell Rep 2020 Mar; 30(11): 3766-3777.e6

Disruption of cyclophilin A (CypA)-capsid interactions affects HIV-1 replication in human lymphocytes. To understand this mechanism, we utilize human Jurkat cells, peripheral blood mononuclear cells (PBMCs), and CD4+ T cells. Our results show that inhibition of HIV-1 infection caused by disrupting CypA-capsid interactions is dependent on human tripartite motif 5α (TRIM5αhu), showing that TRIM5αhu restricts HIV-1 in CD4+ T cells. Accordingly, depletion of TRIM5αhu in CD4+ T cells rescues HIV-1 that fail to interact with CypA, such as HIV-1-P90A. We found that TRIM5αhu binds to the HIV-1 core. Disruption of CypA-capsid interactions fail to affect HIV-1-A92E/G94D infection, correlating with the loss of TRIM5αhu binding to HIV-1-A92E/G94D cores. Disruption of CypA-capsid interactions in primary cells has a greater inhibitory effect on HIV-1 when compared to Jurkat cells. Consistent with TRIM5α restriction, disruption of CypA-capsid interactions in CD4+ T cells inhibits reverse transcription. Overall, our results reveal that CypA binding to the core protects HIV-1 from TRIM5αhu restriction.

https://pubmed.ncbi.nlm.nih.gov/32187548